The polysaccharide K (PSK) potentiates in vitro activation of the cytotoxic function in human blood lymphocytes by autologous tumour cells

Vánky, Farkas; Wang, P.; Klein, E.

doi:10.1007/bf01756187

Cited by 24 publications

(12 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…8 The dose response of PSK ( Figure 1B) showed that 25 g/mL PSK is sufficient to induce SAP. Therefore we used this dose throughout the present experiments.…”

Section: Psk and Trx80 Potentiate T-cell Activation In Ebv-infected Cmentioning

confidence: 94%

“…We decided to use the immunomodulator polysaccharide K (PSK), based on our earlier results in mixed lymphocyte-tumor cell culture in which it potentiated the cellmediated response. 8 PSK is a protein-bound polysaccharide, extracted from the mycelium of Coriolus versicolor. PSK has been used as a immunostimulant for treating cancer patients in Japan for more than 20 years.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12

Liu

Arbiser

Holmgren

et al. 2005

Blood

View full text Add to dashboard Cite

Epstein-Barr virus (EBV)- IntroductionEpstein-Barr virus (EBV) is ubiquitous in the human population. 1 More than 90% of the individuals are virus carriers. The virus persists in spite of EBV-specific humoral and cellular immunity, directed against viral components and against virus-induced cellular proteins. [2][3][4] The outcome of the first encounter with the virus is highly variable. It can occur unnoticed, but if infection is delayed until adolescence it causes the infectious mononucleosis (IM) syndrome in about half of the cases. The IM syndrome is complex, with wide variation in severity, but it is always self-limiting. The decisive mechanism that arrests EBV-induced B-cell proliferation is attributed to both innate and EBV-specific cellular immunity.EBV-specific immunity is not transferred from mother to child. Therefore, cord blood mononuclear cells (CBMCs) are well suited for analysis of cellular interactions in primary infection. Earlier reports showed induction of both natural killer (NK) and CD4 T-cell-mediated cytotoxic activities 5,6 and interleukin-2 (IL-2)-producing CD4 T cells 7 responding to EBV-infected B lymphocytes in cord blood cultures.We have studied previously the events following EBV infection of CBMCs in vitro. We decided to use the immunomodulator polysaccharide K (PSK), based on our earlier results in mixed lymphocyte-tumor cell culture in which it potentiated the cellmediated response. 8 PSK is a protein-bound polysaccharide, extracted from the mycelium of Coriolus versicolor. PSK has been used as a immunostimulant for treating cancer patients in Japan for more than 20 years. 9 Its antitumor activity has been documented in experimental animal models, and beneficial therapeutic effects have been shown in the clinical studies. 9 We reported earlier that in CBMC cultures, the T cells were activated and the outgrowth of EBV-transformed B cells was inhibited if PSK was added. The EBV-infected cultures contained mainly CD4 T cells that acquired cytotoxic function upon restimulation with autologous EBVtransformed B cells. 10 The present work was directed to the analysis of the PSKinduced effects in the EBV-infected CBMC cultures. We assumed that the T cells were activated by encounter with the EBV-infected B lymphocytes, and subsequently they responded to PSK or to factors induced by PSK. We show here that the monocytes became activated by PSK and produced cytokines that acted on T and NK cells. 11,12 Truncated thioredoxin (Trx80), a 10-kDa form of thioredoxin secreted from cells and present in plasma, has been shown to stimulate a T helper 1 (Th1) response in human peripheral blood mononuclear cell (PBMC) cultures through induction of IL-12 production in monocytes. [13][14][15] Based on these earlier findings, we have added Trx80 to the EBV-infected CBMC cultures.We found that T cells were activated in the presence of Trx80, and the EBV-induced B-cell growth was inhibited. Similarly to the effect of PSK, the Trx80-induced growth inhibition was also initiated by the activation of monocyte...

show abstract

“…8 The dose response of PSK ( Figure 1B) showed that 25 g/mL PSK is sufficient to induce SAP. Therefore we used this dose throughout the present experiments.…”

Section: Psk and Trx80 Potentiate T-cell Activation In Ebv-infected Cmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12

Liu

Arbiser

Holmgren

et al. 2005

Blood

View full text Add to dashboard Cite

show abstract

“…PSK induces production of interleukin 8 by reacting with circulating monocytes, and also activates CTLs and causes dendritic cells to mature (3,23,24). In addition, PSK may be able to enhance MHC class I expression by tumor cells (23).…”

Section: Correlation Between Expression Of Mhc Class I and Efficacy Omentioning

confidence: 99%

“…In addition, PSK may be able to enhance MHC class I expression by tumor cells (23). Immunocompetent cells that have been activated by PSK act on trace residual gastric cancer cells of which MHC class I expression has been reduced and bring about recovery of that expression.…”

Section: Correlation Between Expression Of Mhc Class I and Efficacy Omentioning

confidence: 99%

Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Ito

Tanaka

Ohira

et al. 2012

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Protein-bound polysaccharide K (PSK) is a glycoprotein that is purified from the mushroom Coriolus versicolor. In Japan, PSK is clinically used in combination with anticancer agents following gastric cancer surgery. Evaluation of the response is difficult, as efficacy is determined via antitumor immunoenhancing effects, and for that reason PSK has not become a standard therapy. The present study evaluated the expression of MHC class I in gastric cancer patients who received PSK postoperative adjuvant immunochemotherapy, and investigated the correlation between MHC class I expression and clinical outcomes. The subjects comprised 349 patients with stage II/III gastric cancer, who had received adjuvant therapy following curative resection between 1995 and 2008. MHC class I expression in the primary lesion was evaluated by immunohistochemical staining. Patients were divided into two treatment groups: one was only administered oral chemotherapy (chemotherapy-only group) and the other was administered chemotherapy plus PSK (PSK group). The clinical outcomes were compared between the two groups. The two groups did not differ in regard to their MHC class I expression. Expression-negative cases demonstrated 3-year recurrence-free survival (RFS) rates of 65% in the PSK group and 47% in the chemotherapy-only group. Therefore, the PSK group revealed a prolonged survival. For the 82 expressionnegative cases with pN2 or greater, the RFS rates were 68% in the PSK group and 28% in the chemotherapy-only group, representing a significant difference. Thus, PSK adjuvant immunochemotherapy may be effective in MHC class I-negative patients, who are in a state of antitumor immunological tolerance, and patients with advanced lymph node metastasis of pN2 or greater. IntroductionIn Japan, adjuvant therapy using S-1 is considered effective for stage II/III gastric cancer. However, postoperative recurrence is observed in 30% of stage III patients, and the efficacy of S-1 monotherapy is marginal (1). Thus, combination of S-1 with various anticancer agents is being tested. Protein-bound polysaccharide K (PSK) is a glycoprotein extracted from the mushroom Coriolus versicolor belonging to the Polyporaceae family (2). Use of this antitumor agent is approved by the Japanese health insurance system, and has been confirmed to prolong survival in gastric cancer patients. PSK is considered to demonstrate not only direct cytocidal activity, but also antitumor immunoenhancing effects (3,4). However, the mechanisms of these effects remain unclear, and in addition, since 1994 no studies have reported any clinical efficacy of PSK against gastric cancer, thus this agent has not been recognized as a standard therapy (5).The fact that hosts become immunocompromised at the time of tumor progression has long been considered to be significant. In particular, decreased expression of MHC class I by the tumor is one mechanism which allows evasion of cytotoxic T lymphocytes (CTLs), which play a central role in tumor immunity (6). This has been reported t...

show abstract

“…However, this principle is difficult in practice because the most effective anticancer drugs are generally used during primary treatment. A combination of UFT and OK-432 or another combination of anticancer drugs and an immunopotentiator is recommended in distant metastases because drugs possess not only potent cancer cell growth-inhibitory activity but also induce tumor cell apoptosis [45, 46]and cytotoxic lymphocytes [47, 48]required for successful treatment.…”

Section: Discussionmentioning

confidence: 99%

Clinical Investigation on Pulmonary Metastasis of Head and Neck Carcinomas

et al. 2000

View full text Add to dashboard Cite

Objective: To establish a treatment strategy for pulmonary metastases, we clinically investigated the characteristics of distant metastases from head and neck carcinomas. Methods: In 636 head and neck carcinomas, the pathophysiology of distant metastases was investigated by charts, roentgenographies, computed tomographies and scintigraphies. Results: Of the squamous cell carcinomas, oropharyngeal tumors were most highly metastatic, followed by lower gingiva, floor of the mouth, maxillary sinus, and tongue. In distant metastases, 30 (4.7%), 5 (0.8%), and 7 (1.1%) metastasized to the lungs only, lungs and other organs, and organs excluding the lungs, respectively. In pulmonary metastases, the right, left and both lungs were involved in 18, 5, and 8 patients, respectively, although details were not obtained for 4 patients. Pulmonary metastases consisted of 1, 2, and 3 or more tumors in 18, 4, and 6 patients, respectively. Diffuse cancer cell infiltration was observed in 3 patients. Of the 42 patients with distant metastases, 12 patients died of progressive pulmonary metastases, and 5 of these patients manifested only 1 pulmonary lesion throughout life. However, the metastatic pulmonary tumors were controlled surgically or conservatively in 3 patients. Conclusion: These results indicate that distant metastases from head and neck carcinomas involve the lungs most frequently and that chemoimmunotherapy and surgical removal of the metastatic tumors are recommended when indicated.

show abstract

The polysaccharide K (PSK) potentiates in vitro activation of the cytotoxic function in human blood lymphocytes by autologous tumour cells

Cited by 24 publications

References 18 publications

PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12

PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12

Correlation between efficacy of PSK postoperative adjuvant immunochemotherapy for gastric cancer and expression of MHC class I

Clinical Investigation on Pulmonary Metastasis of Head and Neck Carcinomas

Contact Info

Product

Resources

About